Human MAIT‐cell responses to Escherichia coli: activation, cytokine production, proliferation, and cytotoxicity

[摘要] Mucosa‐associatedinvariantTcellsarealargeandrelativelyrecentlydescribedinnate‐likeantimicrobialT‐cellsubsetinhumans.Thesecellsrecognizeriboflavinmetabolitesfromarangeofmicrobespresentedbyevolutionarilyconservedmajorhistocompatibilitycomplex,classI‐relatedmolecules.Giventheinnate‐likecharacteristicsofmucosa‐associatedinvariantTcellsandthenoveltypeofantigenstheyrecognize,newmethodologymustbedevelopedandexistingmethodsrefinedtoallowcomprehensivestudiesoftheirroleinhumanimmunedefenseagainstmicrobialinfection.Inthisstudy,weestablishedprotocolstoexaminearangeofmucosa‐associatedinvariantT‐cellfunctionsastheyrespondtoantigenproducedbyEscherichiacoli.Theseimprovedanddose‐andtime‐optimizedexperimentalprotocolsallowdetailedstudiesofMR1‐dependentmucosa‐associatedinvariantT‐cellresponsestoEscherichiacolipulsedantigen‐presentingcells,asassessedbyexpressionofactivationmarkersandcytokines,byproliferation,andbyinductionofapoptosisanddeathinmajorhistocompatibilitycomplex,classI‐related–expressingtargetcells.Thenovelandoptimizedprotocolsestablishaframeworkofmethodsandopennewpossibilitiestostudymucosa‐associatedinvariantT‐cellimmunobiology,usingEscherichiacoliasamodelantigen.Furthermore,weproposethattheserobustexperimentalsystemscanalsobeadaptedtostudymucosa‐associatedinvariantT‐cellresponsestoothermicrobesandtypesofantigen‐presentingcells...

[学科分类] 生理学

[关键词] MR1;innate‐like T cells;antimicrobial activity;functional evaluation